Single cell transcriptomics identifies distinct profiles in pediatric acute respiratory distress syndrome

Tim Flerlage, Jeremy Chase Crawford, E. Kaitlynn Allen, Danielle Severns, Shaoyuan Tan, Sherri Surman, Granger Ridout, Tanya Novak, Adrienne Randolph, Alina N. West and Paul G. Thomas ()
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Tim Flerlage: St. Jude Children’s Research Hospital
Jeremy Chase Crawford: St. Jude Children’s Research Hospital
E. Kaitlynn Allen: St. Jude Children’s Research Hospital
Danielle Severns: University of Tennessee Health Science Center
Shaoyuan Tan: St. Jude Children’s Research Hospital
Sherri Surman: St. Jude Children’s Research Hospital
Granger Ridout: St. Jude Children’s Research Hospital
Tanya Novak: Critical Care, and Pain Medicine, Boston Children’s Hospital
Adrienne Randolph: Critical Care, and Pain Medicine, Boston Children’s Hospital
Alina N. West: University of Tennessee Health Science Center
Paul G. Thomas: St. Jude Children’s Research Hospital

Nature Communications, 2023, vol. 14, issue 1, 1-18

Abstract: Abstract Acute respiratory distress syndrome (ARDS), termed pediatric ARDS (pARDS) in children, is a severe form of acute respiratory failure (ARF). Pathologic immune responses are implicated in pARDS pathogenesis. Here, we present a description of microbial sequencing and single cell gene expression in tracheal aspirates (TAs) obtained longitudinally from infants with ARF. We show reduced interferon stimulated gene (ISG) expression, altered mononuclear phagocyte (MNP) transcriptional programs, and progressive airway neutrophilia associated with unique transcriptional profiles in patients with moderate to severe pARDS compared to those with no or mild pARDS. We additionally show that an innate immune cell product, Folate Receptor 3 (FOLR3), is enriched in moderate or severe pARDS. Our findings demonstrate distinct inflammatory responses in pARDS that are dependent upon etiology and severity and specifically implicate reduced ISG expression, altered macrophage repair-associated transcriptional programs, and accumulation of aged neutrophils in the pathogenesis of moderate to severe pARDS caused by RSV.

Date: 2023
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DOI: 10.1038/s41467-023-39593-0

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